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1.
Garrison K Hahn T Lee WC Ling LE Weinberg AD Akporiaye ET 《Cancer immunology, immunotherapy : CII》2012,61(4):511-521
Effective tumor immunotherapy may require not only activation of anti-tumor effector cells, but also abrogation of tumor-mediated
immunosuppression. The cytokine TGF-β, is frequently elevated in the tumor microenvironment and is a potent immunosuppressive
agent and promoter of tumor metastasis. OX40 (CD134) is a member of the TNF-α receptor superfamily and ligation by agonistic
antibody (anti-OX40) enhances effector function, expansion, and survival of activated T cells. In this study, we examined
the therapeutic efficacy and anti-tumor immune response induced by the combination of a small molecule TGF-β signaling inhibitor,
SM16, plus anti-OX40 in the poorly immunogenic, highly metastatic, TGF-β-secreting 4T1 mammary tumor model. Our data show
that SM16 and anti-OX40 mutually enhanced each other to elicit a potent anti-tumor effect against established primary tumors,
with a 79% reduction in tumor size, a 95% reduction in the number of metastatic lung nodules, and a cure rate of 38%. This
positive treatment outcome was associated with a 3.2-fold increase of tumor-infiltrating, activated CD8+ T cells, an overall accumulation of CD4+ and CD8+ T cells, and an increased tumor-specific effector T cell response. Complete abrogation of the therapeutic effect in vivo
following depletion of CD4+ and CD8+ T cells suggests that the anti-tumor efficacy of SM16+ anti-OX40 therapy is T cell dependent. Mice that were cured of their
tumors were able to reject tumor re-challenge and manifested a significant tumor-specific peripheral memory IFN-γ response.
Taken together, these data suggest that combining a TGF-β signaling inhibitor with anti-OX40 is a viable approach for treating
metastatic breast cancer. 相似文献
2.
Yang Liu Jing Cai Wenfeng Liu Yuan Lin Li Guo Xincheng Liu Zhen Qin Cuiying Xu Yanming Zhang Xingwen Su Kai Deng Guangmei Yan Jiankai Liang 《Cell death & disease》2020,11(12)
Reversing the highly immunosuppressive tumor microenvironment (TME) is essential to achieve long-term efficacy with cancer immunotherapy. Despite the impressive clinical response to checkpoint blockade in multiple types of cancer, only a minority of patients benefit from this approach. Here, we report that the oncolytic virus M1 induces immunogenic tumor cell death and subsequently restores the ability of dendritic cells to prime antitumor T cells. Intravenous injection of M1 disrupts immune tolerance in the privileged TME, reprogramming immune-silent (cold) tumors into immune-inflamed (hot) tumors. M1 elicits potent CD8+ T cell-dependent therapeutic effects and establishes long-term antitumor immune memory in poorly immunogenic tumor models. Pretreatment with M1 sensitizes refractory tumors to subsequent checkpoint blockade by boosting T-cell recruitment and upregulating the expression of PD-L1. These findings reveal the antitumor immunological mechanism of the M1 virus and indicated that oncolytic viruses are ideal cotreatments for checkpoint blockade immunotherapy.Subject terms: Cancer microenvironment, Targeted therapies 相似文献
3.
The idea of immunological surveillance against cancer has existed for nearly 100 years but as no conclusive evidence has yet
been published the importance of the cellular immune defense in the detection and removal of incipient or existing tumors
is still a hotly debated subject. However, in order to select a relevant immunotherapeutic strategy in the treatment of cancer,
a fundamental understanding of the basic immunologic conditions under which a tumor develops and exists is a prerequisite.
Therefore, a murine model was set up that we hoped would enable us to confirm or reject the theory of immunological surveillance.
A large panel of methylcholanthrene induced tumors was established in T-cell immunodeficient nude mice and congenic normal
mice to study the influence of the immune system on developing tumors. As nude mice developed tumors fastest and with the
highest incidence, we concluded that in this model the immune system constituted a ‘tumor-suppressive factor’ delaying and
sometimes abrogating tumor growth, i.e. performing immune surveillance. Immunogenicity of the tumors was assessed by transplantation
back to normal histocompatible mice. Tumors originating from the immunodeficient nude mice turned out to be far more immunogenic
than tumors from normal mice, resulting in a high rejection rate. CD8+cytotoxic T cells were found to be indispensable for
this rejection, leading to the conclusion that the cytotoxic T cells perform immune selection in normal mice, eliminating
immunogenic tumor cell variants in the incipient tumor.
In this review, we discuss the difficulties facing immunotherapy when conclusions are drawn from the presented observations
and hypotheses. 相似文献
4.
5.
Kobayashi H Nagato T Aoki N Sato K Kimura S Tateno M Celis E 《Cancer immunology, immunotherapy : CII》2006,55(7):850-860
The product of Wilms‘ tumor gene 1 (WT1) is overexpressed in diverse human tumors, including leukemia, lung and breast cancer,
and is often recognized by antibodies in the sera of patients with leukemia. Since WT1 encodes MHC class I-restricted peptides
recognized by cytotoxic T lymphocytes (CTL), WT1 has been considered as a promising tumor-associated antigen (TAA) for developing
anticancer immunotherapy. In order to carry out an effective peptide-based cancer immunotherapy, MHC class II-restricted epitope
peptides that elicit anti-tumor CD4+ helper T lymphocytes (HTL) will be needed. In this study, we analyzed HTL responses against WT1 antigen using HTL lines elicited
by in vitro immunization of human lymphocytes with synthetic peptides predicted to serve as HTL epitopes derived from the
sequence of WT1. Two peptides, WT1124–138 and WT1247–261, were shown to induce peptide-specific HTL, which were restricted by frequently expressed HLA class II alleles. Here, we
also demonstrate that both peptides-reactive HTL lines were capable of recognizing naturally processed antigens presented
by dendritic cells pulsed with tumor lysates or directly by WT1+ tumor cells that express MHC class II molecules. Interestingly,
the two WT1 HTL epitopes described here are closely situated to known MHC class I-restricted CTL epitopes, raising the possibility
of stimulating CTL and HTL responses using a relatively small synthetic peptide vaccine. Because HTL responses to TAA are
known to be important for promoting long-lasting anti-tumor CTL responses, the newly described WT1 T-helper epitopes could
provide a useful tool for designing powerful vaccines against WT1-expressing tumors. 相似文献
6.
Background
Surgery and radiation are the mainstays of therapy for human gliomas that are the most common primary brain tumors. Most recently, cell culture and animal studies provided the first convincing evidence that radiation not only eliminates tumor cells, but also modulates the immune response and likely improves anti-tumor immunotherapy.Methology/Pricipal Findings
We present an in vivo study that analyzes the effects of radiation on the immune response in tumor patients. As readout system, we utilized the reactivity of glioma patients'' sera against antigen GLEA2 as the most frequent antigen immunogenic in glioblastoma patients. We established an ELISA assay to analyze reactivity of 24 glioblastoma patients over a period of several months. As control we used 30 sera from healthy donors as well as 30 sera from lung cancer patients. We compared the course of GLEA2 seroreactivity at different times prior, during and after radiation. The GLEA2 seroreactivity was increased by the time of surgery, decreased after surgery, increased again under radiation, and slightly decreased after radiation.Conclusions/Significance
Our results provide in vivo evidence for an increased antibody response against tumor antigens under radiation. Antigens that become immunogenic with an increased antibody response as result of radiation can serve as ideal targets for immunotherapy of human tumors. 相似文献7.
Ping Gao Xiaolei Sun Xing Chen John Subjeck Xiang-Yang Wang 《Cancer immunology, immunotherapy : CII》2009,58(8):1319-1328
It is well established that certain stress proteins or molecular chaperones are highly efficient in cross-presenting tumor-derived
antigens, resulting in a potent antitumor immune response. In this study we demonstrate that genetic modification of weakly
immunogenic murine prostate tumor cells (TRAMP-C2) by stable transfection with a secretable form of endoplasmic reticulum
resident chaperone grp170 significantly enhances its immunogenicity in vivo. Generation of systemic antitumor immunity is
indicated by the growth suppression of distant parental tumors, which is associated with increased tumor infiltration, elevated
effector functions of CD8+ T-cells. Immunization with inactivated grp170-secreting C2 cells augments a CD8+ T-cell dependent, tumor-protective effect. Furthermore, infection of C2 tumor cells with a nonreplicating adenoviral vectors
encoding secretable grp170 promotes tumor immunogenicity more effectively than plasmid transduction, as shown by the increased
production of pro-inflammatory cytokine TNF-α by dendritice cells and enhanced therapeutic efficacy in treating pre-established
tumors. Given a repertoire of undefined antigens in prostate tumor, manipulation of cellular compartmentalization of immuno-stimulatory
chaperone grp170 to elicit systemic tumor immunity may be used to improve treatment outcomes for prostate cancer when combined
with other treatment modalities. 相似文献
8.
Laure Delavallée Luca Semerano Eric Assier Géraldine Vogel Grégoire Vuagniaux Marion Laborie Daniel Zagury Natacha Bessis Marie-Christophe Boissier 《Arthritis research & therapy》2009,11(6):R195
Introduction
Passive blockade of tumor necrosis factor-alpha (TNF-α) has demonstrated high therapeutic efficiency in chronic inflammatory diseases, such as rheumatoid arthritis, although some concerns remain such as occurrence of resistance and high cost. These limitations prompted investigations of an alternative strategy to target TNF-α. This study sought to demonstrate a long-lasting therapeutic effect on established arthritis of an active immunotherapy to human (h) TNF-α and to evaluate the long-term consequences of an endogenous anti-TNF-α response. 相似文献9.
Metastatic diseases cause the majority of morbidity and mortality of cancer patients. Established tumors form both physical and immunological barriers to limit immune detection and destruction. Current immunotherapy of vaccination and adoptive transfer shows limited effect at least in part due to the existing barriers in the tumors and depending on the knowledge of tumor antigens. Tumor necrosis factor (TNF) superfamily (TNFSF) member 14 (TNFSF14) LIGHT interacts with stromal cells, dendritic cells (DCs), NK cells, na?ve and activated T cells and tumor cells inside the tumor tissues via its two functional receptors, HVEM and lymphotoxin beta receptor (LTbetaR). Targeting tumor tissues with LIGHT leads to augmentation of priming, recruitment, and retention of effector cells at tumor sites, directly or indirectly, to induce strong anti-tumor immunity to inhibit the growth of primary tumors as well as eradicate metastases. Intratumor treatment would break tumor barriers and allow strong immunity against various tumors without defining tumor antigens. This review summarizes recent findings to support that LIGHT is a promising candidate for an effective cancer immunotherapy. 相似文献
10.
Immunotherapeutic approaches to cancer should focus on novel undertakings that modulate immune responses by synergistic enhancement
of anti-tumor immunological parameters. Cancer vaccines should preferably be composed of multiple defined tumor antigen specific
B- and T-cell epitopes. The main focus of this article is to briefly review the present status of Her-2/neu vaccine strategies
and to describe the innovative strategies developed in my laboratory for a vaccine against HER-2/neu (ErbB-2) with emphasis
on the humoral arm of the immune response. Elucidating the underlining mechanisms of anti-tumor effects elicited by peptide
vaccines against a self-protein is a requirement for developing an immunotherapeutic strategy that might be effective in human
cancer vaccines. Our approach entails the identification of biologically relevant epitopes, establishing relevant in vitro assays for monitoring vaccine efficacy, devising strategies to engineer conformationally dependent sequences, developing
highly immunogenic vaccines for an outbred population and delivering the immunogen/vaccine in a safe and efficacious vehicle,
utilizing transgenic animal models for assessing tumor development, and developing challenge models using transplantable tumors
to study efficacy of vaccine constructs. We have developed a multi-HER-2/neu B-cell epitope approach and shown in preclinical
studies that immunization with a combination of two B-cell epitope was more effective in preventing mammary tumors than a
single epitope. We have translated that work to the clinic (OSU 0105) in an FDA approved, NCI sponsored “Phase 1 Active Immunotherapy trial with Chimeric and Multi-epitope based peptide vaccine targeting HER-2 oncoprotein and
nor-MDP adjuvant in patients with metastatic and/or recurrent solid tumors” at the James Cancer Hospital at the Ohio State University. The correlation between overexpression of HER-2/neu and up-regulation of VEGF has been demonstrated in breast cancer patients. Thus, blocking angiogenesis is an attractive strategy
to inhibit tumor growth, invasion, and metastasis. The hypothesis that combination of anti-angiogenic therapy and tumor immunotherapy
of cancer may be synergistic is an important future goal. In this review, I will discuss insights into our preclinical studies
that might aid in the design of the next generation of cancer vaccines and become an integrated component of prophylactic/preventive
and therapeutic approach. 相似文献
11.
Sandy Pelletier Simon Tanguay Stephen Lee Lakshman Gunaratnam Nathalie Arbour Réjean Lapointe 《Cancer immunology, immunotherapy : CII》2009,58(8):1207-1218
Objectives Patients with renal cell carcinomas (RCC) have few treatment options, underscoring the importance of developing new approaches
such as immunotherapy. However, few tumor associated antigens (TAA), which can be targeted by immunotherapy, have been identified
for this type of cancer. von Hippel-Lindau clear cell RCC (VHL−/−RCC) are characterized by mutations in the VHL tumor suppressor gene. Loss of VHL function causes the overexpression of transforming
growth factor (TGF)-α, leading us to hypothesize that TGF-α could be a potential TAA for immunotherapy of kidney cancer, which
was evaluated in this study.
Methods and results We first confirmed the absent or weak expression of TGF-α in important normal tissues as well as its overexpression in 61%
of renal tumors in comparison to autologous normal kidney tissues. In addition, we demonstrated the immunogenicity of TGF-α,
by expanding many T cell lines specific for certain TGF-α peptides or the mature TGF-α protein, when presented by major histocompatibility
complex (MHC) molecules on the surface of antigen-presenting cells. Interestingly, some of these TGF-α-specific T cells were
polyfunctionals and secreted IFN-γ, TNF-α and IL-2.
Conclusion We have shown that TGF-α is a valid candidate TAA, which should allow the development of a targeted immunotherapy. 相似文献
12.
Successful treatment of cancer patients with a combination of monoclonal antibodies (mAb) and chemotherapeutic drugs has spawned
various other forms of additional combination therapies, including vaccines or adoptive lymphocyte transfer combined with
chemotherapeutics. These therapies were effective against established tumors in animal models and showed promising results
in initial clinical trials in cancer patients, awaiting testing in larger randomized controlled studies. Although combination
between immunotherapy and chemotherapy has long been viewed as incompatible as chemotherapy, especially in high doses meant
to increase anti-tumor efficacy, has induced immunosuppression, various mechanisms may explain the reported synergistic effects
of the two types of therapies. Thus direct effects of chemotherapy on tumor or host environment, such as induction of tumor
cell death, elimination of regulatory T cells, and/or enhancement of tumor cell sensitivity to lysis by CTL may account for
enhancement of immunotherapy by chemotherapy. Furthermore, induction of lymphopenia by chemotherapy has increased the efficacy
of adoptive lymphocyte transfer in cancer patients. On the other hand, immunotherapy may directly modulate the tumor’s sensitivity
to chemotherapy. Thus, anti-tumor mAb can increase the sensitivity of tumor cells to chemotherapeutic drugs and patients treated
first with immunotherapy followed by chemotherapy showed higher clinical response rates than patients that had received chemotherapy
alone. In conclusion, combination of active specific immunotherapy or adoptive mAb or lymphocyte immunotherapy with chemotherapy
has great potential for the treatment of cancer patients which needs to be confirmed in larger controlled and randomized Phase
III trials. 相似文献
13.
Takumi Kumai Kei Ishibashi Kensuke Oikawa Yoshinari Matsuda Naoko Aoki Shoji Kimura Satoshi Hayashi Masahiro Kitada Yasuaki Harabuchi Esteban Celis Hiroya Kobayashi 《Cancer immunology, immunotherapy : CII》2014,63(5):469-478
Posttranslational modifications regulate the function and stability of proteins, and the immune system is able to recognize some of these modifications. Therefore, the presence of posttranslational modifications increases the diversity of potential immune responses to a determinant antigen. The stimulation of tumor-specific CD4+ helper T lymphocytes (HTLs) is considered important for the production of anti-tumor antibodies by B cells and for the generation and persistence of CD8+ cytotoxic T lymphocytes, and in some instances, HTLs can directly reduce tumor cell growth. Identification of MHC class II-restricted peptide epitopes from tumor-associated antigens including those generated from posttranslational protein modifications should enable the improvement of peptide-based cancer immunotherapy. We describe here an MHC class II binding peptide from the tumor protein p53, which possesses an acetylated lysine at position 120 (p53110-124/AcK120) that is effective in eliciting CD4+ T cell responses specific for the acetylated peptide. Most importantly, the acetylated peptide-reactive CD4 HTLs recognized the corresponding naturally processed posttranslational modified epitope presented by either dendritic cells loaded with tumor cell lysates or directly on tumors expressing p53 and the restricting MHC class II molecules. Treatment of tumor cells with a histone deacetylase inhibitor augmented their recognition by the p53110-124/AcK120-reactive CD4+ T cells. These findings prove that the epitope p53110-124/AcK120 is immunogenic for anti-tumor responses and is likely to be useful for cancer immunotherapy. 相似文献
14.
Yona Keisari Ilan Hochman Hila Confino Rafi Korenstein Itzhak Kelson 《Cancer immunology, immunotherapy : CII》2014,63(1):1-9
Cancer, the most devastating chronic disease affecting humankind, is treated primarily by surgery, chemotherapy, and radiation therapy. Surgery and radiotherapy are mainly used for debulking the primary tumor, while chemotherapy is the most efficient anti-metastatic treatment. To control better metastatic cancer, the host immune system should be stimulated. Yet, successful specific stimulation of the immune system against tumors was seldom achieved even in antigenic tumors. Our working hypothesis is that aggressive in situ tumor ablation can release tumor antigens and danger signals, which will enhance anti-tumor T cell responses resulting in the destruction of residual malignant cells in primary tumors and distant metastases. We developed two efficient in situ ablation treatments for solid cancer, which can be used to destroy the primary tumors and stimulate anti-tumor immune responses. The first treatment, electrochemical ablation, is applied through intratumoral electrodes, which deliver unipolar-pulsed electric currents. The second treatment, diffusing alpha-emitters radiation therapy (DaRT), is based on intratumoral 224Ra-loaded wire(s) that release by recoil its daughter atoms. These short-lived alpha-emitting atoms spread in the tumor and spray it with lethal alpha particles. It was confirmed that these treatments effectively destroy various malignant animal and human primary solid tumors. As a consequence of such tumor ablation, tumor-derived antigenic material was released and provoked systemic T cell-dependent anti-tumor immunological reactions. These reactions conferred protection against a secondary tumor challenge and destroyed remaining malignant cells in the primary tumor as well as in distant metastases. Such anti-tumor immune responses could be further amplified by the immune adjuvant, CpG. Electrochemical ablation or DaRT together with chemotherapy and immunostimulatory agents can serve as treatment protocols for solid metastatic tumors and can be applied instead of or in combination with surgery. 相似文献
15.
Chih-Chun Wen Hui-Ming Chen Swey-Shen Chen Li-Ting Huang Wei-Ting Chang Wen-Chi Wei Li-Chen Chou Palanisamy Arulselvan Jin-Bin Wu Sheng-Chu Kuo Ning-Sun Yang 《Journal of biomedical science》2011,18(1):1-15
Background
Damage-associated molecular patterns (DAMPs) are associated with immunogenic cell death and have the ability to enhance maturation and antigen presentation of dendritic cells (DCs). Specific microtubule-depolymerizing agents (MDAs) such as colchicine have been shown to confer anti-cancer activity and also trigger activation of DCs.Methods
In this study, we evaluated the ability of three MDAs (colchicine and two 2-phenyl-4-quinolone analogues) to induce immunogenic cell death in test tumor cells, activate DCs, and augment T-cell proliferation activity. These MDAs were further evaluated for use as an adjuvant in a tumor cell lysate-pulsed DC vaccine.Results
The three test phytochemicals considerably increased the expression of DAMPs including HSP70, HSP90 and HMGB1, but had no effect on expression of calreticulin (CRT). DC vaccines pulsed with MDA-treated tumor cell lysates had a significant effect on tumor growth, showed cytotoxic T-lymphocyte activity against tumors, and increased the survival rate of test mice. In vivo antibody depletion experiments suggested that CD8+ and NK cells, but not CD4+ cells, were the main effector cells responsible for the observed anti-tumor activity. In addition, culture of DCs with GM-CSF and IL-4 during the pulsing and stimulation period significantly increased the production of IL-12 and decreased production of IL-10. MDAs also induced phenotypic maturation of DCs and augmented CD4+ and CD8+ T-cell proliferation when co-cultured with DCs.Conclusions
Specific MDAs including the clinical drug, colchicine, can induce immunogenic cell death in tumor cells, and DCs pulsed with MDA-treated tumor cell lysates (TCLs) can generate potent anti-tumor immunity in mice. This approach may warrant future clinical evaluation as a cancer vaccine. 相似文献16.
Several vectors, viral and bacterial, have been developed over the past few years for means of generating an effective antitumor
immune response. We have developed and studied a “model for immunotherapy” using a viral vector disabled infectious single
cycle-herpes simplex virus (DISC-HSV), which efficiently transduces various tumor cell lines and offers a useful vehicle for
the further development of cell-based vaccines. The immunotherapeutic potential of DISC-HSV encoding granulocyte macrophage
colony stimulating factor (GM-CSF) was demonstrated in a number of murine carcinoma models, leading to complete regression
of well-established tumors in up to 70% of the mice. Moreover, the therapeutic potential of DISC-HSV-GM-CSF was significantly
enhanced when used in combination therapy with either OX40L or dendritic cells (DC), even in a poorly immunogenic tumor model.
The ability of this vector to accept large gene inserts, its good safety profile, its ability to undergo only a single round
of infection, the inherent viral immunostimulatory properties and its ability to infect various tumor cell lines efficiently,
make DISC-HSV an ideal candidate vector for immunotherapy. The DISC- CT-26 tumor model was used to investigate the mechanisms
associated with immunotherapy induced tumor rejection. Although CTL induction, was positively correlated with regression,
MHC class I down regulation and accumulation of immature Gr1+ myeloid cells were shown to be the main immuno-suppressor mechanisms
operating against regression and associated with progressive tumor growth. The CTL response was associated with the immuno-dominant
AH-1 peptide of the retroviral glycoprotein gp70. This model of immunotherapy has provided an opportunity to dissect further
the immunological events associated with tumor-rejection and escape. Since other antigens may be important in initiating tumor
rejection, we have investigated the expression of MTA-1, an antigen that appears to be expressed widely in human and murine
tumors. The immunogenicity of MTA-1 was studied and its potential as a tumor rejection antigen is under investigation.
This article is a symposium paper from the conference "Progress in Vaccination against Cancer 2004 (PIVAC 4)", held in Freudenstadt-Lauterbad,
Black Forest, Germany, on 22–25 September 2004. 相似文献
17.
Parviz M Chin CS Graham LJ Miller C Lee C George K Bear HD 《Cancer immunology, immunotherapy : CII》2003,52(12):739-750
Tumor cell vaccines have been successful at inducing immunity in naïve mice, but only in a few reports has vaccination alone induced regression of established tumors and, generally, only when they are very small. Clinically, vaccinations alone may not be able to cause regression of established human cancers, which tend to be weakly immunogenic. We hypothesized that pharmacologic ex vivo amplification of a vaccination-induced immune response with subsequent adoptive immunotherapy (AIT) to tumor-bearing animals would be more effective in treatment of these animals than vaccination alone. The 4T1 and 4T07 mammary carcinomas are derived from the same parental cell line, but 4T1 is much less immunogenic and more aggressive than 4T07. Vaccination with either 4T1, 4T1-IL-2, or 4T07-IL-2 was not effective as treatment for established 4T1 tumors. However, 4T1 or 4T07-IL-2-vaccine-sensitized draining lymph node (DLN) cells, activated ex vivo with bryostatin 1 and ionomycin and expanded in culture, induced complete tumor regressions when adoptively transferred to 4T1 tumor-bearing animals. This was effective against small tumors as well as more advanced tumors, 10 days after tumor cell inoculation. Furthermore, as would be required for this approach to be used clinically, vaccine-DLN cells obtained from mice with established progressive 4T1 tumors (inoculated 10 days before vaccination) also induced regression of 4T1 tumors in an adoptive host. In none of these experiments was exogenous IL-2 required to induce tumor regression. The response to tumor cell vaccine can be amplified by ex vivo pharmacologic activation of sensitized T cells, which can then cure an established, weakly immunogenic and highly aggressive tumor that was resistant to vaccination alone. 相似文献
18.
Therapeutic effectiveness of the immunity elicited by P815 tumor cells engineered to express the B7-2 costimulatory molecule 总被引:2,自引:0,他引:2
Ross N. La Motte Michael A. Rubin Eliav Barr Jeffrey M. Leiden Jeffrey A. Bluestone M. B. Mokyr 《Cancer immunology, immunotherapy : CII》1996,42(3):161-169
It is well accepted that inoculation of B7-1-transfected tumor cells into normal mice leads to tumor rejection and subsequent
resistance to challenge. However, the effectiveness of B7-2-transfected tumor cells in eliciting protective antitumor immunity
is less clear. Here we show that B7-2-transfected P815 tumor cells (B7-2+) are as effective as B7-1-transfected P815 tumor cells (B7-1+) in eliciting protective immunity in normal DBA/2 mice. In addition, B7-2+ cells were found to be at least as effective as B7-1+ cells in retarding tumor progression when admixed with parental P815 tumor cells prior to inoculation into normal mice. Moreover,
the B7-2+ cells and the B7-1+ cells were equivalent in their ability to retard tumor growth when administered peritumorally into mice bearing established
(approx. 3 mm in diameter) parental P815 tumors. Finally, P815 tumor cells infected with a recombinant replication-defective
adenovirus encoding the murine B7-2 gene were effective in retarding the growth of established parental P815 tumors. Thus,
B7-1 and B7-2 are comparable in terms of their ability to stimulate the generation of tumor-eradicating immunity in normal
mice as well as in mice bearing established parental tumors. Moreover, adenovirus vectors can be used to generate B7-2-expressing
tumor cells effective in the immunotherapy of established parental tumors.
Received: 10 January 1996 / Accepted: 23 February 1996 相似文献
19.
Da-Yong Cao Jing-Yue Yang Shu-Qiang Yue Zhen-Shun Song Yan-Ling Yang 《Cellular immunology》2009,259(1):13-20
Fusions of patient-derived dendritic cells (DCs) and autologous tumor cells induce T-cell responses against autologous tumors in animal models and human clinical trials. These fusion cells require patient-derived tumor cells, which are not, however, always available. Here we fused autologous DCs from patients with hepatocellular carcinoma (HCC) to an allogeneic HCC cell line (HepG2). These fusion cells co-expressed tumor-associated antigens (TAAs) and DC-derived costimulatory and MHC molecules. Both CD4+ and CD8+ T cells were activated by the fusion cells. Cytotoxic T lymphocytes (CTLs) induced by the fusion cells were able to kill autologous HCC by HLA-A2- and/or HLA-A24-restricted mechanisms. CTL activity against shared TAAs indicates that the presence of alloantigens does not prevent the development of CTLs with activity against autologous HCC cells. These fusion cells may have applications in anti-tumor immunotherapy through cross-priming against shared tumor antigens and may provide a platform for adoptive immunotherapy. 相似文献
20.
Fenella J. Rich Sabine Kuhn Evelyn J. Hyde Jacquie L. Harper Franca Ronchese Joanna R. Kirman 《Cancer immunology, immunotherapy : CII》2012,61(12):2333-2342
Mycobacteria and their cell wall components have been used with varying degrees of success to treat tumors, and Mycobacterium bovis BCG remains in use as a standard treatment for superficial bladder cancer. Mycobacterial immunotherapy is very effective in eliciting local immune responses against solid tumors when administered topically; however, its effectiveness in eliciting adaptive immune responses has been variable. Using a subcutaneous mouse thymoma model, we investigated whether immunotherapy with Mycobacterium smegmatis, a fast-growing mycobacterium of low pathogenicity, induces a systemic adaptive immune response. We found that M. smegmatis delivered adjacent to the tumor site elicited a systemic anti-tumor immune response that was primarily mediated by CD8+ T cells. Of note, we identified a CD11c+CD40intCD11bhiGr-1+ inflammatory DC population in the tumor-draining lymph nodes that was found only in mice treated with M. smegmatis. Our data suggest that, rather than rescuing the function of the DC already present in the tumor and/or tumor-draining lymph node, M. smegmatis treatment may promote anti-tumor immune responses by inducing the involvement of a new population of inflammatory cells with intact function. 相似文献